Glial cells: much more than the tail of neurons

It is very common that when we talk about a person’s intelligence, we refer specifically to a very specific type of cell: neurons. Thus, it is normal to call mononeuronal which is attributed a low intelligence in a pejorative way. however, the idea that the brain is essentially equivalent to a set of neurons is increasingly outdated.

The human brain contains over 80 billion neurons, but that is only 15% of the total number of cells in this set of organs.

The remaining 85% are occupied by another type of microscopic body: the so-called glial cells. Overall, these cells they form a substance called glia or neuroglia, Which extends to all corners of the nervous system.

Glia is currently one of the most advanced fields of study in neuroscience. looking to reveal all his tasks and the interactions they perform to make the nervous system work the way it does. And it is that the brain cannot currently be understood without understanding the implication of the glia.

The discovery of glial cells

The term neuroglia was coined in 1856 by German pathologist Rudolf Virchow. It is a word which means in Greek “neural glue (glia)”, as at the time of its discovery neurons were thought to come together to form nerves and, further, that the axon was a collection of cells rather than part of the neuron. Therefore, it was speculated that these cells found near neurons must help structure the nerve and facilitate connection between them, and nothing more. A rather passive and auxiliary role, in short.

In 1887, the famous researcher Santiago Ramón i Cajal came to the conclusion that neurons were independent units and were separated from each other by a small space known later as the synaptic space. This served to disprove the idea that axons were more than parts of independent nerve cells. However, the idea of ​​the passivity of the glia has remained. Today, however, we discover that its importance is much greater than it should be.

In a way, it is ironic that the name given to the neuroglia is as follows. It is true that while it helps in the structure, but not only performs this function, but also for its protection, repairing damage, improving nerve impulses, providing energy and even controlling the flow of information, among many many other features discovered. They are a powerful tool for the nervous system.

Types of glial cells

The neuroglia is a collection of different types of cells that have in common that are in the nervous system and are not neurons.

There are several types of glial cells, but I will focus on the four classes considered to be the most important, as well as the most important functions discovered to date. As I said, this area of ​​neuroscience is advancing more and more and there will certainly be new details unknown today.

1. Schwann cells

The name of this glia cell is in honor of its discoverer, Theodor Schwann, better known as one of the fathers of cell theory. This type of glial cell is the only one present in the peripheral nervous system (PNS), that is, in the nerves that run throughout the body.

Studying the anatomy of nerve fibers in animals, Schwann observed cells that attach themselves along the axon and appear to be like little “pearls”; beyond that, he gave them no more importance. In future studies, it was discovered that these microscopic beaded elements were in fact myelin sheaths, an important product that generates this type of cell.

Myelin is a lipoprotein that it provides isolation against the electrical impulse in the axonIn other words, it allows the action potential to be maintained for longer and at a greater distance, which speeds up electrical traits and does not disperse across the membrane of the neuron. In other words, they act like the rubber covering a cable.

Schwann cells have the ability to secrete several neurotrophic components, including ‘nerve growth factor’ (FCN)The first growth factor is found in the nervous system. This molecule is used to stimulate the growth of neurons during development. In addition, since this type of neuroglia surrounds the axon as if it were a tube, it also has an influence on the marking of the direction in which it should develop.

Beyond that, it was seen that when damage was done to a nerve in the SNP, FCN is secreted so that the neuron can regrow and regain its functionality. This explains the process by which the temporary paralysis that muscles experience after suffering a fracture goes away.

The three different Schwann cells

For early anatomists there were no differences in Schwann cells, but with advances in microscopy up to three different types could be differentiated, with well differentiated structures and functions. The ones I have described are “myelin” because they produce myelin and are the most common.

however, in neurons with short axons there is another type of Schwann cell called ‘amyelin’., As it does not produce myelin sheaths. These are larger than the previous ones and inside they house more than one axon at a time. Apparently, they don’t produce myelin sheaths, because with their own membrane, it already serves as an insulator for these smaller axons.

The last type of this form of neuroglia is found in the synapse between neurons and muscles. They are known as terminal or perisynaptic Schwann cells (Enter the synapse). The function which is currently entrusted to him was revealed thanks to the experiment carried out by Richard Robitaille, 1 neurobiologist at the University of Montreal. The test was to add a fake messenger to these cells to see what was going on. The result was that the response expressed by the muscle was altered. In some cases the contraction increased, in other cases it decreased. The conclusion was that this type of glia regulates the flow of information between the neuron and the muscle.

2. Oligodendrocytes

There are no Schwann cells in the central nervous system (CNS), but neurons have another form of myelin coating through another type of glial cell. This function is performed by the last of the main types of neuroglia discovered: that formed by oligodendrocytes.

Their name refers to how they were described by the first anatomists who found them; a cell with a multitude of small extensions. But the truth is that the name does not accompany them much, because a time later a pupil of Ramon and Cajal, Pie de la Rivière-Hortega, devised improvements in the coloring used at the time, revealing the true morphology. : a cell with a pair of long extensions, as if they were arms.

Myelin in the CNS

A difference between oligodendrocytes and Schwann’s myelin cells is that the former do not envelop the axon with their body, but they do it with their long extensions, as if they were tentacles of an octopus, And it is for them that myelin is secreted. In addition, the myelin in the CNS does not serve only to isolate the neuron.

As Martin Schwab demonstrated in 1988, the deposition of myelin on the axon in cultured neurons hinders its growth. In search of an explanation, Schwab and his team were able to purify several myelin proteins at the origin of this inhibition: Nogo, MAG and OMgp. The funny thing is that we have seen that in the early stages of brain development, the myelin MAG protein stimulates neuronal growth, performing a reverse function on the neuron in adults. The reason for this inhibition is a mystery, but scientists hope its role will soon be known.

Another protein found in myelin in the 1990s, this time by Stanley B. Prusiner, is also found in myelin: the prion protein (PrP). Its function in the normal state is unknown, but in the mutated state it becomes a prion and generates a variant of Creutzfeldt-Jakob disease, commonly known as mad cow disease. The prion is a protein that gains autonomy, infecting all glial cells, which generates neurodegeneration..

3. Astrocytes

This type of glial cell has been described by Ramón and Cajal. During his observations of neurons, he noticed that near the neurons were other cells, in the shape of a star; hence its name. It is located in the CNS and the optic nerve, and is probably one of the glia that performs the most functions.. Its size is two to ten times the size of a neuron, and it has very different functions.

Blood brain barrier

Blood does not donate directly to the CNS. This system is protected by the blood-brain barrier (BBB), a highly selective permeable membrane. Astrocytes are actively involved, be responsible for filtering out what can happen on the other side and what cannot. Mainly, they allow the entry of oxygen and glucose, to be able to feed the neurons.

But what if that barrier is broken? In addition to the problems generated by the immune system, groups of astrocytes move to the damaged area and join together to form a temporary barrier and stop the bleeding.

Astrocytes have the ability to synthesize a fibrous protein known as GFAP, with which they gain robustness, as well as to secrete another set of proteins which allows them to gain impermeability. In parallel, the astrocytes secrete neurotrophs, to stimulate the regeneration of the area.

Recharge the potassium battery

Another of the described functions of astrocytes is their activity to maintain the action potential. When a neuron generates an electrical impulse, it collects sodium ions (Na +) to become more positive with the outside. This process by which electrical charges are manipulated from outside and inside neurons produces a state known as depolarization, which causes electrical impulses that pass through the neuron to end up in the synaptic space. During your trip, the cell medium always seeks equilibrium in the electric charge, so that this time it loses potassium ions (K +), To match the extracellular environment.

If this still happened, in the end a saturation of potassium ions would be generated on the outside, which would mean that these ions would stop coming out of the neuron, resulting in the inability to generate the electrical impulse. This is where astrocytes come in. they absorb these ions inside to cleanse the extracellular space and allow more potassium ions to continue to be secreted.. Astrocytes have no problem with charging because they do not communicate by electrical impulses.

4. Microglia

The last of the four most important forms of neuroglia is the microglia. This was discovered before oligodendrocytes, but it was thought to originate from blood vessels. It occupies between 5 and 20% of the glia population of the CNS, And its importance is based on the fact that it is the basis of the brain’s immune system. With the protection of the blood-brain barrier, the free passage of cells is not allowed, including those of the immune system. For that, the brain needs its own defense system, and this is made up of this type of glia.

The CNS immune system

This glia cell has great mobility, which allows you to react quickly to any problem you are having in the CNS. Microglia have the ability to devour damaged cells, bacteria and viruses, as well as release a number of chemicals with which to fight invaders. But the use of these elements can cause collateral damage, as it is also toxic to neurons. Therefore, after the confrontation, they have to produce, like astrocytes do, neurotrophs to facilitate regeneration of the affected area.

I have already talked about the damage to the BBB, a problem caused in part by the side effects of microglia when white blood cells pass through the BBB and get inside the brain. Inside the CNS is a new world for these cells, and above all they react as unknown as if it were a threat, generating an immune response against it. Microglia initiates defense, causing what we might call a “civil war”, Which causes a lot of damage to neurons.

Communication between glia and neurons

As you have seen, glial cells perform a variety of tasks. But one section that has not become clear is whether the neurons and the neuroglia are communicating with each other. The first researchers have already realized that the glia, unlike neurons, does not generate electrical impulses. But that changed when Stephen J. Smith checked out how they communicated, both with each other and with neurons..

Smith had the intuition that the neuroglia uses the calcium ion (Ca2 +) to transmit information, because this element is most commonly used by cells in general. Somehow, he and his teammates threw themselves into the pool with this conviction (after all, an ion’s “popularity” doesn’t tell us much about their specific functions either), but they got it right.

These researchers designed an experiment that consisted of a culture of astrocytes to which fluorescent calcium was added, which allows fluorescence microscopy to see its position. Plus, he added a very common neurotransmitter, glutamate, to the middle. The result was not long in coming. For ten minutes they could see fluorescence entering astrocytes and moving between cells as if it were a wave. With this experiment, they showed that the glia communicate with each other and with the neuron, because without the neurotransmitter, the wave does not start.

The last known about glial cells

Through more recent research, it has been discovered that glia detects all types of neurotransmitters. Additionally, astrocytes and microglia have the ability to make and release neurotransmitters (although these elements are called gliotransmitters because they originate from the glia), thus influencing the synapses of neurons.

A current field of study is to see upwards where glial cells influence the overall functioning of the brain and that of complex mental processes, Such as learning, memory or sleep.

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